Comamonas spp. are non-fermenting Gram-negative bacilli. They were first discovered in 1894, and since then, twenty-four species have been characterized. The natural habitat of these bacteria is soil, wastewater/sludge, fresh water such as ponds and rivers, and the animal intestinal microbiome. They were also isolated from industrial settings, such as activated sludge and polluted soil, and from the hospital environment and clinical samples, such as urine, pus, blood, feces, and kidney. Comamonas spp. are associated with environmental bioremediation and are considered an important environmental bacterium rather than a human pathogen. However, in the 1980s, they became a concern when several human infections associated with these species were reported. Here, the Comamonas genus was examined in terms of its members, identification techniques, and pathogenicity. Seventy-seven infection cases associated with these microorganisms that have been discussed in the literature were identified and investigated in this project. All relevant information regarding year of infection, country of origin, patient information such as age, sex, underlying medical conditions if any, type of infection caused by the Comamonas species, antibiotic susceptibility testing, treatment, and outcomes for the patient were extracted from case reports. The findings suggest that even though Comamonas spp. are thought of as being of low virulence, they have caused harmful health conditions in many healthy individuals and even death in patients with underlying conditions. Antimicrobial treatment of infections associated with these species, in general, was not very difficult; however, it can become an issue in the future because some strains are already resistant to different classes of antibiotics. Therefore, these pathogens should be considered of such importance that they should be included in the hospital screening programs.